Cardiac enlargement is considered to be a compensatory action in response to chronic overload stress and is commonly found in patients having valvular disorders or severe hypertension. Because the total quantity of cardiac muscle cell nuclear material remains fixed in the enlarged adult heart, the possibility exists that failure of the cardiac muscle cell to replicate its complement of nuclear material may represent a "rate limiting" condition. Experimental conditions have been identified where cardiac muscle cell division does occur during adaptive heart growth in neonatal animals. Therefore, the proposed work will employ experimental models in which cardiac enlargement is achieved either with or without cardiac muscle cell division and define factors which appear likely to regulate DNA synthesis and cell division during adaptive heart growth. Once these factors have been identified, it may be possible to initiate appropriate interventions which will modify heart cell division. The ability to increase the total complement of cardiac muscle cell nuclear DNA could alleviate many of the "rate limiting" conditions encountered during cardiac enlargement and exert profound beneficial influences on myocardial function.